Hypertension and Hypercholesterolemia Modify Dementia Risk in Relation to APOEɛ4 Status

Article type: Research Article

Authors: Pillai, Jagan A.^{a; b; c; *} | Kou, Lei^{d; 1} | Bena, James^{d; 1} | Penn, Lisa^a | Leverenz, James B.^{a; b; c}

Affiliations: [a] Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA | [b] Neurological Institute and Cleveland Clinic, Cleveland, OH, USA | [c] Department of Neurology, Cleveland Clinic, Cleveland, OH, USA | [d] Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

Correspondence: [*] Correspondence to: Jagan A Pillai, MBBS, PhD, Staff Neurologist, Lou Ruvo Center for Brain Health, Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 9500 Euclid Ave / U10, Cleveland, OH 44195, USA. Tel.: +1 216 636 9467; Fax: +1 216 445 7013; pillaij@ccf.org.

Note: [1] Statistical analysis conducted by Lei Kou, MA, and James Bena, MS, Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.

Abstract: Background:There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Objective:Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOE ɛ4 carriers and non-carriers. Methods:In a sample of prospectively characterized longitudinal cohort from the National Alzheimer’s Coordinating Center database, 9,349 participants met criteria for normal cognition at baseline, had a CDR-Global (CDR-G) score of zero, and had concomitant data on APOE ɛ4 status and medical co-morbidities including histories of hypertension and hypercholesterolemia. Multivariable Cox proportional hazards models adjusted for well-known potential confounders were used to compare dementia onset among APOE ɛ4 carriers and non-carriers by young (≤65 years) and old (> 65 year) age groups. Results:519 participants converted to dementia within an average follow up of 5.97 years. Among older APOE ɛ4 carriers, hypercholesterolemia was related to lower risk of dementia (HR (95% CI), 0.68 (0.49–0.94), p = 0.02). Among older APOE ɛ4 non-carriers, hypertension was related to higher risk of dementia (HR (95% CI), 1.44 (1.13–1.82), p = 0.003). These results were corroborated among a subset with autopsy data characterizing underlying neuropathology. Among younger participants, vascular risk factors did not impact dementia risk, likely from a lower frequency of vascular and Alzheimer’s as etiologies of dementia among this cohort. Conclusion:A history of hypercholesterolemia related to a lower risk of dementia among older APOE ɛ4 carriers, while hypertension related to a higher risk of dementia among older APOE ɛ4 non-carriers.

Keywords: APOE ɛ4, dementia, dementia risk, depression, hypercholesterolemia, hypertension, longitudinal cohort study, mixed dementia, neuropathology, normal cognition cohort

DOI: 10.3233/JAD-201609

Journal: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1493-1504, 2021